Dietary intake of Ca can vary widely among individuals and from day to day. Assuming an intake of 1000 mg (the RDA for ages 19–50), 350 mg would typically be absorbed, counterbalanced by 150 mg secreted by the intestine, for a net intake of 200 mg. Most Ca++ absorption takes place in the proximal small intestine. Importantly, absorption of Ca++ is stimulated by 1,25-dihydroxyvitamin D, so absorption is more efficient in the face of declining dietary Ca++ .
Ca++ is absorbed from the duodenum and jejunum by both a Ca++-regulated and a hormonally regulated transcellular route and by a passive paracellular route. The transcellular route of Ca++ absorption is summarized in
Fig.
40.8 . Movement of Ca++ from the gastrointestinal lumen into the enterocyte, which is driven by both chemical and electrical gradients, occurs via apical calcium channels called TRPV5 and TRPV6. Once inside the cell, Ca++ ions bind to calbindin-D9K, which maintains a low cytoplasmic [Ca++], preserving the favorable transluminal membrane Ca++ gradient. Calbindin-D9K also plays a role in apical-to-basolateral shuttling of Ca++, which is transported across the basolateral membrane against an electrochemical gradient by plasma membrane calcium ATPase (PMCA). The Na+/Ca++ exchanger (NCX) also contributes to the
CASR,calcium-sensingreceptor;M-CSF,monocytecolony-stimulatingfactor;NPT2,Na+/Picotransporter;OPG,osteoprotegerin;PTH,parathyroidhormone;
RANKL,receptoractivatorofnuclearfactorκ-B.
•Fig. 40.8 IntestinalabsorptionofCa++viathetranscellularroute.(ModifiedfromPorterfieldSP,WhiteBA.Endocrine Physiology. 3rded.Philadelphia:Mosby;2007.)LuminalsideTRPV5/6SerosalsideCa++Ca++Ca++Ca++-cal indin9KCal indin9KPMCA transport of Ca++ out of enterocyte. 1,25-Dihydroxyvitamin D stimulates expression of all the components involved in absorption of Ca++ by the small intestine.
The fraction of dietary Pi absorbed by the jejunum remains relatively constant at about 70% and is under minor hormonal control by 1,25-dihydroxyvitamin D. The limiting process in transcellular Pi absorption is transport across the apical brush border, which is mediated by the Na+/Pi cotransporter (NPT2).
Bone stores vast amounts of Ca and Pi. Once peak bone mass has been achieved in an adult, the skeleton is constantly remodeled through the concerted activities of bone cells. The processes of bone formation and bone resorption are in balance in a healthy, physically active, and well-nourished individual. Of the 1 kg of Ca immobilized in bone, about 500 mg (i.e., 0.5%) is mobilized from and deposited into bone each day. However, the process of bone remodeling can be modulated to provide a net gain or loss of Ca++ and Pi into blood and is responsive to physical activity (loading), diet, age, and hormonal regulation. Because the integrity of bone is absolutely dependent on Ca and Pi, chronic dysregulation of these ions or the hormones that regulate them lead to pathological changes in bone.
Physiology of Bone
The processes of pattern formation, growth, and remodeling of the skeleton is complex and beyond the scope of this chapter. The key elements required for understanding the role of adult bone in the hormonal regulation of Ca and Pi metabolism are discussed.